Tissue macrophages and their precursor, peripheral blood monocytes, are important mediators in resistance to infection, rejection of grafts and tumors and processing of antigen. The process of activation whereby monocytes and macrophages becomes more efficient metabolically and functionally is poorly understood. Changes in the levels of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) have been shown to mediate control of many immune functions. Cyclic nucleotide levels are in turn controlled through activation or inhibition of cyclase enzymes which synthesize and phosphodiesterases which degrade cAMP and cGMP. The role of cyclic nucleotides in control of normal monocyte and macrophage function and particularly in activation of these cells is unknown. The purpose of this study is to correlate the content and metabolism of cAMP and cGMP with monocyte and macrophage function. The importance of changes in content will be assessed by measuring the levels of cGMP by radioimmunoassay in resting, phagocytic and activated states. Elucidation of the mechanisms through which macrophage cyclic nucleotide levels are controlled will involve studies of the subcellular location and kinetics of adenyl and guanyl cyclases and, if necessary, of cyclic nucleotide phosphodiesterases. The effect of in vivo and in vitro activation of monocytes and macrophages on these cyclic nucleotide parameters will be examined with special emphasis on the effects of immunotherapeutic (BCG, levamisole, MER) and cytoreductive (corticosteroids) agents used in the therapy of acute leukemia and other tumors.